1. Field of the Invention
Photodynamic therapy (PDT) is a technique used for treating several types of diseases, in particular, certain types of cancer. Such a technique consists of marking the pathological tissues with a photosensitizer, then causing selective destruction of said tissues while exposing them to a light source of a specific wavelength. Such monochromatic light is generally produced by a laser or a laser diode.
2. Description of Related Art Including Information Disclosed Under 37 CFR 1.97 and 37 CFR 1.98
A photosensitizer is understood to mean any molecule liable to store light energy, being activated by said energy and lending itself therefore to numerous biochemical combinations.
The photosensitizer, generally between 0.1 and 0.5 micromole/kg of body mass, is delivered to the patient, then picked up by the cells of the whole organism. The photosensitizing molecule accumulates preferably in cancerous cells, but remains inactive until exposed to a light of appropriate wavelength. The illumination or irradiation of the tumour by light activates the molecule, which then interacts with oxygen and forms a transient substance, in particular singlet oxygen. Singlet oxygen is a very reactive and toxic molecule which destroys the cancerous cells wherein the photosensitizer has concentrated.
A certain time elapses between the delivery of the photosensitizer and its activation by means of the laser light. The laser light used in photodynamic therapy is focused by means of an optic fiber and is applied only for a few minutes. The practitioner holds the optic fiber in close vicinity of the cancer so as to deliver the correct amount of light. Consequently, photodynamic therapy only damages the healthy cells minimally.
At the initial stage of a cancer, the objective of such a technique may consist of completely eliminating and curing the cancer but, at an advanced stage, it may consist of reducing the volume of the tumour in order to alleviate symptoms. New normal cells replace those destroyed by photodynamic therapy, which enables rapid healing after treatment and avoids particularly ungracious scars which may form with other ablation of tissues.
Even patients already treated by surgery, radiotherapy or chemotherapy may be subjected to this technique reliably.
By way of examples of diseases which may be treated by photodynamic therapy, one may quote in particular stomach, intestine, lung, breast, uterus, esophagus, ovary, pancreas, liver, bladder, bile, tongue, brain, skin, thyroid, prostate, parotid gland cancer, as well as certain viral and/or microbial diseases.
Photodynamic therapy may also be used as a means for diagnosing certain forms of cancer. In this view, it suffices that the photosensitizing molecules are fluorescent and, hence, capable of emitting light when they receive a radiation.
At the moment, the use of certain porphyrin derivatives, in particular hematoporphyrin, as photosensitizers is known in photodynamic therapy. This agent, known under the trademark Photofrin™, registered by AXCAN PHARMA INC., is a purified mixture of hematoporphyrin. Hematoporphyrin is in turn a derivative of porcine hemoglobin.
Besides, Photofrin™ has been the sole photosensitizing molecule until now, which has been authorized for marketing in several countries and, in particular, in France, for treating esophageal cancer.
In spite of the advantages shown by Photofrin™, such as its solubility in an aqueous medium, a good output of singlet oxygen formation and an easy synthesis, it still exhibits a few shortcomings.
First of all, Photofrin™ is activated by a 630 nm light. Still, at such a wavelength, the penetration of light into the tissues only ranges from 5 to 10 mm, which exhibits a severe handicap when tumours are wider and deeper. Moreover, such a photosensitizer causes cutaneous photosensitivity up to six weeks after treatment. Finally, the fact, that Photofrin™ is a mixture of several molecules, makes the choice of the appropriate dosimetry more difficult, as well as the choice of the photosensitizer of the light delivered.
Among other compounds under study, so-called second generation compounds, the document WO-98/50386 describes certain benzoporphyrine derivatives. Such derivatives exhibit certain advantages relative to Photofrin™ in that they absorb light at a 690 nm wavelength and, consequently, may be used in the treatment of wider and deeper cancers. Such derivates exhibit moreover better selectivity against cancerous cells.
However, certain problems associated with selectivity, light absorption and toxicity persist.